WO1995014475A1 - The use of an ester of inositoltrisphosphate for the preparing of medicaments - Google Patents
The use of an ester of inositoltrisphosphate for the preparing of medicaments Download PDFInfo
- Publication number
- WO1995014475A1 WO1995014475A1 PCT/SE1994/001091 SE9401091W WO9514475A1 WO 1995014475 A1 WO1995014475 A1 WO 1995014475A1 SE 9401091 W SE9401091 W SE 9401091W WO 9514475 A1 WO9514475 A1 WO 9514475A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hiv
- ester
- inositoltrisphosphate
- myo
- cells
- Prior art date
Links
- 150000002148 esters Chemical class 0.000 title claims abstract description 28
- 239000003814 drug Substances 0.000 title claims abstract description 25
- MMWCIQZXVOZEGG-XJTPDSDZSA-N D-myo-Inositol 1,4,5-trisphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=O MMWCIQZXVOZEGG-XJTPDSDZSA-N 0.000 title claims abstract description 19
- MMWCIQZXVOZEGG-UHFFFAOYSA-N 1,4,5-IP3 Natural products OC1C(O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(O)C1OP(O)(O)=O MMWCIQZXVOZEGG-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 230000001177 retroviral effect Effects 0.000 claims abstract description 5
- 208000030507 AIDS Diseases 0.000 claims description 12
- 150000003839 salts Chemical group 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 3
- 208000012124 AIDS-related disease Diseases 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 description 26
- 241000725303 Human immunodeficiency virus Species 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 208000015181 infectious disease Diseases 0.000 description 16
- 125000003118 aryl group Chemical group 0.000 description 14
- 125000000753 cycloalkyl group Chemical group 0.000 description 13
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 125000003710 aryl alkyl group Chemical group 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- -1 isocyano, carboxy Chemical group 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 208000031886 HIV Infections Diseases 0.000 description 6
- 102100034349 Integrase Human genes 0.000 description 6
- 125000002877 alkyl aryl group Chemical group 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 6
- 229960002555 zidovudine Drugs 0.000 description 6
- 208000037357 HIV infectious disease Diseases 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 108010047620 Phytohemagglutinins Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000001885 phytohemagglutinin Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 229960000367 inositol Drugs 0.000 description 3
- 230000002045 lasting effect Effects 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- 101710121417 Envelope glycoprotein Proteins 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000001388 Opportunistic Infections Diseases 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000005864 Sulphur Chemical group 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 125000005024 alkenyl aryl group Chemical group 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000005499 phosphonyl group Chemical group 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XSSYCIGJYCVRRK-RQJHMYQMSA-N (-)-carbovir Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1C[C@H](CO)C=C1 XSSYCIGJYCVRRK-RQJHMYQMSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108010010369 HIV Protease Proteins 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 0 O=C(CC1)*C1=O Chemical compound O=C(CC1)*C1=O 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- IHBCFWWEZXPPLG-UHFFFAOYSA-N [Ca].[Zn] Chemical compound [Ca].[Zn] IHBCFWWEZXPPLG-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- CDAISMWEOUEBRE-JMVOWJSSSA-N cis-inositol Chemical compound O[C@@H]1[C@H](O)[C@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-JMVOWJSSSA-N 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- CDAISMWEOUEBRE-NIPYSYMMSA-N epi-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)[C@H]1O CDAISMWEOUEBRE-NIPYSYMMSA-N 0.000 description 1
- XHDPYSCXPWDZQX-UHFFFAOYSA-N ethyl-di(propan-2-yl)azanium;hydrogen phosphate Chemical compound OP([O-])([O-])=O.CC[NH+](C(C)C)C(C)C.CC[NH+](C(C)C)C(C)C XHDPYSCXPWDZQX-UHFFFAOYSA-N 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 230000000652 homosexual effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002032 methanolic fraction Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- CDAISMWEOUEBRE-GNIYUCBRSA-N muco-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@H]1O CDAISMWEOUEBRE-GNIYUCBRSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100001222 nononcogenic Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 108010086652 phytohemagglutinin-P Proteins 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 108010043277 recombinant soluble CD4 Proteins 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- CDAISMWEOUEBRE-CDRYSYESSA-N scyllo-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O CDAISMWEOUEBRE-CDRYSYESSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/117—Esters of phosphoric acids with cycloaliphatic alcohols
Definitions
- HIV infects human cells primarily by binding to CD4 receptors on the surface of susceptible cells. This binding is mediated by the oligomeric envelope glycoprotein (gp) of HIV and the receptor on the target cell surface followed by the fusion between the viral envelope and the plasma membrane.
- the post- binding events which lead to membrane fusion are poorly understood but presumably include a conformational change in the envelope protein which exposes the hydrophopic a ino terminus of a gp 41 envelope protein in the fusion reaction.
- the binding of the HIV-1 envelope glycoprotein, gp 120, to the cellular receptor is the first step in HIV infection.
- CD4 independent mechanism of infection There are reports of HIV infection in a number of CD4-negative cells in vitro (Harouse, J.M. et al., J. Virol, 63, 2527, 1989, Zachar, V.B. et al. J. Virol, 65, 2102, 1991).
- zidovudine was found to have in vitro activity against the human immunodeficiency virus, HIV.
- the in vitro and clinical activity of zidovudine is not disputed, but there is considerable debate when to initiate treatment (J.G. Bartlett, : New Engl. J. of Med. , 329, 351, 1993; Cooper D.A. et al.: New Engl. J. of Med., 329, 297, 1993).
- nucleoside analogues are on trial but these will probably only be of limited usage as the mode of action including side effects reinforcee those of zidovudine.
- AZT The function of AZT is to block the action of the enzyme reverse transcriptase of HIV which stops the virus from replicating in the cells.
- ester of inositoltris ⁇ phosphate used for the preparing of the medicament according to the invention are present in salt form in order not to affect the mineral balance negatively.
- the salt should preferably consist of a sodium, potassium, calcium zinc or magnesium salt or a mixture of two or more of these salts.
- X is a radical of myo-inositol or a configura ⁇ tion isomer thereof.
- lower alkyl such as methyl, ethyl or propyl.
- R Q y is a substituted or unsubstituted, straight or branched alkyl, cycloalkyl, aryl or aralkyl; preferably n is 1 or 2 and R is a lower alkyl such as methyl, ethyl or propyl.
- n is an integer between 1 and 10 and where R Q y is a substituted or unsubstitu- ted, straight or branched alkyl, cycloalkyl, aryl or aralkyl and where R is hydrogen or substituted or unsubstituted, straight or branched alkyl, cyclo ⁇ alkyl, aryl or aralkyl; preferably n is l, R is lower y alkyl such as methyl, ethyl or propyl and R is hydrogen.
- H 9 cells Three preparations of H 9 cells were chronically infected by HIV-3B (type code of HIV-virus) and mixed with uninfected C 8166 cells. This mixture formed a number of syncytia-cells with more than five nucleus and ballooning cytoplasm.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51499095A JP3769011B2 (ja) | 1993-11-22 | 1994-11-18 | イノシトール三燐酸エステルの薬剤調製への使用 |
| US08/648,175 US5846957A (en) | 1993-11-22 | 1994-11-18 | Use of an ester of inositoltrisphosphate for the preparing of medicaments |
| EP95901674A EP0730459B1 (de) | 1993-11-22 | 1994-11-18 | Verwendung eines inositoltriphosphatester, zur herstellung eines medikamentes |
| AT95901674T ATE232387T1 (de) | 1993-11-22 | 1994-11-18 | Verwendung eines inositoltriphosphatester, zur herstellung eines medikamentes |
| AU10816/95A AU1081695A (en) | 1993-11-22 | 1994-11-18 | The use of an ester of inositoltrisphosphate for the preparing of medicaments |
| DE69432124T DE69432124D1 (de) | 1993-11-22 | 1994-11-18 | Verwendung eines inositoltriphosphatester, zur herstellung eines medikamentes |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9303853A SE502989C2 (sv) | 1993-11-22 | 1993-11-22 | Användning av en inositoltrisfosfatester för beredning av läkemedel |
| SE9303853-7 | 1993-11-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995014475A1 true WO1995014475A1 (en) | 1995-06-01 |
Family
ID=20391828
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/SE1994/001091 WO1995014475A1 (en) | 1993-11-22 | 1994-11-18 | The use of an ester of inositoltrisphosphate for the preparing of medicaments |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5846957A (de) |
| EP (1) | EP0730459B1 (de) |
| JP (1) | JP3769011B2 (de) |
| AT (1) | ATE232387T1 (de) |
| AU (1) | AU1081695A (de) |
| DE (1) | DE69432124D1 (de) |
| SE (1) | SE502989C2 (de) |
| WO (1) | WO1995014475A1 (de) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997049408A1 (en) * | 1996-06-24 | 1997-12-31 | Perstorp Ab | The use of growth factor modulating compounds |
| WO1998044935A2 (en) * | 1997-04-09 | 1998-10-15 | Viron Corporation | Antiviral composition containing oxidized inositol, sodium sulfite, pyrocatechol and copper sulfate |
| WO1998057620A2 (en) * | 1997-06-16 | 1998-12-23 | Cedars-Sinai Medical Center | Inositol for modulation of immune response |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2383673T3 (es) * | 2000-09-22 | 2012-06-25 | Jpi Commercial, Llc | Composiciones de gamma-hidroxibutirato que contienen portadores de hidrato de carbonos |
| FR2828206B1 (fr) * | 2001-08-03 | 2004-09-24 | Centre Nat Rech Scient | Utilisation d'inhibiteurs des lysyl oxydases pour la culture cellulaire et le genie tissulaire |
| US7084115B2 (en) | 2002-04-29 | 2006-08-01 | Oxyplus, Inc. | Inositol pyrophosphates, and methods of use thereof |
| US20060106000A1 (en) * | 2004-07-06 | 2006-05-18 | Claude Nicolau | Use of inositol-tripyrophosphate in treating tumors and diseases |
| US20060258626A1 (en) * | 2004-07-06 | 2006-11-16 | Claude Nicolau | Use of inositol-tripyrophosphate in treating tumors and diseases |
| US7745423B2 (en) * | 2004-07-06 | 2010-06-29 | NormOxys, Inc | Calcium/sodium salt of inositol tripyrophosphate as an allosteric effector of hemoglobin |
| WO2006102060A1 (en) * | 2005-03-18 | 2006-09-28 | Oxyplus, Inc. | Calcium salt of myo-inositol 1,6:2,3:4,5 tripyrophosphate as an allosteric effector of hemoglobin |
| AU2008246061A1 (en) * | 2007-05-01 | 2008-11-06 | Normoxys, Inc. | Erythropoietin complementation or replacement |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0269105A2 (de) * | 1986-11-26 | 1988-06-01 | Perstorp Ab | Cyclohexan-Derivate, sie enthaltende Zusammensetzungen und ihre Verwendung |
| WO1989003220A1 (en) * | 1987-10-06 | 1989-04-20 | Houston Biotechnology Incorporated | Phosphatidyl treatment of viral disease |
| WO1990000057A1 (en) * | 1988-06-30 | 1990-01-11 | Shamsuddin Abulkalam M | Reduction of cell proliferation and enhancement of nk-cell activity |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5023248A (en) * | 1984-10-23 | 1991-06-11 | Perstorp Ab | Method of treating diabetes with inositol triphosphate |
| US5015634A (en) * | 1986-04-16 | 1991-05-14 | Perstorp Ab | Method of treating tissue damage with inositol triphosphate |
| US5330979A (en) * | 1984-10-23 | 1994-07-19 | Perstorp Ab | Method of treating renal disorders with inositoltriphosphate |
| US5407924A (en) * | 1984-10-23 | 1995-04-18 | Perstorp Ab | Method of treating pain using inositol triphosphate |
| US5545632A (en) * | 1984-10-23 | 1996-08-13 | Perstorp Ab | Method of treating retroviral disease |
| US5128332A (en) * | 1984-10-23 | 1992-07-07 | Perstorp Ab | Method of treating cardiovascular diseases using inositoltrisphosphate |
| SE465951B (sv) * | 1984-10-23 | 1991-11-25 | Perstorp Ab | Isomer av inositoltrifosfat foeretraedesvis i saltform foer anvaendning som terapeutiskt eller profylaktiskt medel samt kompositioner daerav |
| SE465305B (sv) * | 1986-04-16 | 1991-08-26 | Perstorp Ab | Anvaendning av inositolfosfat foer framstaellning av ett laekemedel |
| US5057507A (en) * | 1986-04-16 | 1991-10-15 | Perstorp Ab | Method of alleviating bone damage with inositoltriphosphate |
| US5135923A (en) * | 1986-04-16 | 1992-08-04 | Perstorp Ab | Method of treating cardiovascular diseases |
-
1993
- 1993-11-22 SE SE9303853A patent/SE502989C2/sv not_active IP Right Cessation
-
1994
- 1994-11-18 US US08/648,175 patent/US5846957A/en not_active Expired - Fee Related
- 1994-11-18 EP EP95901674A patent/EP0730459B1/de not_active Expired - Lifetime
- 1994-11-18 AU AU10816/95A patent/AU1081695A/en not_active Abandoned
- 1994-11-18 DE DE69432124T patent/DE69432124D1/de not_active Expired - Lifetime
- 1994-11-18 WO PCT/SE1994/001091 patent/WO1995014475A1/en active IP Right Grant
- 1994-11-18 AT AT95901674T patent/ATE232387T1/de not_active IP Right Cessation
- 1994-11-18 JP JP51499095A patent/JP3769011B2/ja not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0269105A2 (de) * | 1986-11-26 | 1988-06-01 | Perstorp Ab | Cyclohexan-Derivate, sie enthaltende Zusammensetzungen und ihre Verwendung |
| WO1989003220A1 (en) * | 1987-10-06 | 1989-04-20 | Houston Biotechnology Incorporated | Phosphatidyl treatment of viral disease |
| WO1990000057A1 (en) * | 1988-06-30 | 1990-01-11 | Shamsuddin Abulkalam M | Reduction of cell proliferation and enhancement of nk-cell activity |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997049408A1 (en) * | 1996-06-24 | 1997-12-31 | Perstorp Ab | The use of growth factor modulating compounds |
| EP1216705A2 (de) * | 1996-06-24 | 2002-06-26 | Perstorp Ab | Verwendung von Verbindungen zur Modulation von Wachstumsfaktoren, die durch drei vicinale phosphorhaltige Radikale substituiert sind, zur Herstellung eines Medikaments für die Gewebeerneuerung |
| EP1216705A3 (de) * | 1996-06-24 | 2003-11-12 | Perstorp Ab | Verwendung von Verbindungen zur Modulation von Wachstumsfaktoren, die durch drei vicinale phosphorhaltige Radikale substituiert sind, zur Herstellung eines Medikaments für die Gewebeerneuerung |
| WO1998044935A2 (en) * | 1997-04-09 | 1998-10-15 | Viron Corporation | Antiviral composition containing oxidized inositol, sodium sulfite, pyrocatechol and copper sulfate |
| WO1998044935A3 (en) * | 1997-04-09 | 1998-12-30 | Viron Corp | Antiviral composition containing oxidized inositol, sodium sulfite, pyrocatechol and copper sulfate |
| WO1998057620A2 (en) * | 1997-06-16 | 1998-12-23 | Cedars-Sinai Medical Center | Inositol for modulation of immune response |
| WO1998057620A3 (en) * | 1997-06-16 | 1999-03-18 | Cedars Sinai Medical Center | Inositol for modulation of immune response |
Also Published As
| Publication number | Publication date |
|---|---|
| DE69432124D1 (de) | 2003-03-20 |
| JP3769011B2 (ja) | 2006-04-19 |
| ATE232387T1 (de) | 2003-02-15 |
| AU1081695A (en) | 1995-06-13 |
| JPH09505579A (ja) | 1997-06-03 |
| SE9303853L (sv) | 1995-05-23 |
| SE9303853D0 (sv) | 1993-11-22 |
| SE502989C2 (sv) | 1996-03-04 |
| EP0730459A1 (de) | 1996-09-11 |
| US5846957A (en) | 1998-12-08 |
| EP0730459B1 (de) | 2003-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Piantadosi et al. | Synthesis and evaluation of novel ether lipid nucleoside conjugates for anti-HIV-1 activity | |
| Baba et al. | Potent and selective inhibition of human immunodeficiency virus type 1 (HIV-1) by 5-ethyl-6-phenylthiouracil derivatives through their interaction with the HIV-1 reverse transcriptase. | |
| US4357324A (en) | Prodrug derivatives of 9β-D-arabinofuranosyl-2-fluoroadenine | |
| JP4782365B2 (ja) | ウイルス感染症と癌細胞を二重ターゲッティングする組成物及び方法 | |
| EA019419B1 (ru) | Фосфонатные аналоги соединений ингибиторов вич, фармацевтическая композиция и набор, их включающие, и способ лечения нарушений, ассоциированных с вич | |
| EP0730459B1 (de) | Verwendung eines inositoltriphosphatester, zur herstellung eines medikamentes | |
| IE860677L (en) | Antiviral formulation | |
| US5036103A (en) | Method of treating cancer cells in humans | |
| US5545632A (en) | Method of treating retroviral disease | |
| US4452800A (en) | Salts of 3(n-butyl)-4-hydroxy-1-phenyl-1,8-naphthyridine-2(1H)-one and their use in treating chronic obstructive lung diseases | |
| EP0730460B1 (de) | Verwendung eines inositoltriphosphatesters zur behandlung von entzündungen | |
| CZ181098A3 (cs) | Fosfolipidové deriváty fosfonokarboxylových kyselin, jejich výroba a jejich použití jako antivirového léčiva | |
| Hostetler et al. | Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice | |
| WO1989004314A1 (en) | Anti-viral compounds and compositions containing them | |
| RU2178418C2 (ru) | Ковалентные конъюгаты липидов с фосфонокарбоновой кислотой, их получение и применение в качестве антивирусных лекарственных средств | |
| WO1995010285A1 (en) | The use of inositoltrisphosphate for the preparing of medicaments | |
| EP0365139A2 (de) | Gallensäuren zur Behandlung viraler Infektionen | |
| US4966895A (en) | Cyclic monophosphates of purine and pyrimidine acyclonucleosides as anti-retroviral agents | |
| EP0623623B1 (de) | Komplex von 2-aminoäthansulfonsäure und zink | |
| JPH07504170A (ja) | 抗ウイルス性活性を有するヒペリシン化合物のイオン対 | |
| EP0653206A1 (de) | Anti-hiv-wirkstoff | |
| EP0730461A1 (de) | Verwendung eines inositoltriphosphatesters zur herstellung eines analgetikums | |
| JPH07509442A (ja) | ウィルス病処置でのホスホリル化フラボノイド類 | |
| WO1993023390A1 (en) | 6-pyridyl substituted pyrimidine derivatives and their use as antiviral agents | |
| CS248003B2 (cs) | Způsob výroby derivátů 9-hydroxyethoxymethylguaninu |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AM AT AU BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU JP KE KG KP KR KZ LK LR LT LU LV MD MG MN MW NL NO NZ PL PT RO RU SD SE SI SK TJ TT UA US UZ VN |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE MW SD SZ AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 08648175 Country of ref document: US |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1995901674 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1995901674 Country of ref document: EP |
|
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| NENP | Non-entry into the national phase |
Ref country code: CA |
|
| WWG | Wipo information: grant in national office |
Ref document number: 1995901674 Country of ref document: EP |